title: Hematopoietic growth factor inducible neurokinin-1 (Gpnmb/Osteoactivin) is a biomarker of progressive renal injury across species.
abstract: We sought to find a urinary biomarker for chronic kidney disease and tested hematopoietic growth factor inducible neurokinin-1 (HGFIN, also known as Gpnmb/Osteoactivin) as it was found to be a kidney injury biomarker in microarray studies. Here, we studied whether HGFIN is a marker of kidney disease progression. Its increase in kidney disease was confirmed by real-time PCR after 5/6 nephrectomy, in streptozotocin-induced diabetes, and in patients with chronic kidney disease. In the remnant kidney, HGFIN mRNA increased over time reflecting lesion chronicity. HGFIN was identified in the infarct portion of the remnant kidney in infiltrating hematopoietic interstitial cells, and in distal nephron tubules of the viable remnant kidney expressed de novo with increasing time. In vitro, it localized to cytoplasmic vesicles and cell membranes. Epithelial cells lining distal tubules and sloughed luminal tubule cells of patients expressed HGFIN protein. The urine HGFIN-to-creatinine ratio increased over time after 5/6 nephrectomy; increased in patients with proteinuric and polycystic kidney disease; and remained detectable in urine after prolonged freezer storage. The urine HGFIN-to-creatinine ratio compared favorably with the urine neutrophil gelatinase-associated lipocalin (NGAL)-to-creatinine ratio (both measured by commercial enzyme-linked immunosorbent assays (ELISAs)), and correlated strongly with proteinuria, but weakly with estimated glomerular filtration rate and serum creatinine. Thus, HGFIN may be a biomarker of progressive kidney disease.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California 90502, USA.
authors.forename: Mina
authors.initials: M
authors.lastname: Patel-Chamberlin
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Bancha
authors.initials: B
authors.lastname: Satirapoj
authors.forename: Lynetta M
authors.initials: LM
authors.lastname: Phillips
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Nast
authors.forename: Tiane
authors.initials: T
authors.lastname: Dai
authors.forename: Renecia A
authors.initials: RA
authors.lastname: Watkins
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.forename: Rama
authors.initials: R
authors.lastname: Natarajan
authors.forename: Aishe
authors.initials: A
authors.lastname: Leng
authors.forename: Kathleene
authors.initials: K
authors.lastname: Ulanday
authors.forename: Raimund R
authors.initials: RR
authors.lastname: Hirschberg
authors.forename: Janine
authors.initials: J
authors.lastname: Lapage
authors.forename: Edouardo J
authors.initials: EJ
authors.lastname: Nam
authors.forename: Tahmina
authors.initials: T
authors.lastname: Haq
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Adler
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D009392:Nephrectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D015415:Biomarkers; C503042:GPNMB protein, human; C503043:Gpnmb protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013311:Streptozocin; D003404:Creatinine